We have conducted a randomized, double blind placebo controlled study of surgery with or without raloxifene for treatment of pain from endometriosis. Women with chronic pelvic pain and no endometriosis treatment for 6 months have undergone laparoscopic excision of endometriosis lesions after monitoring pelvic pain for 1 month. Those with biopsy-proven endometriosis were randomized to daily raloxifene (180 mg) or placebo for six months. Return of pain was defined as 2 months of pain severity equal to that at study entry. Women had a second surgery at 2 years, or when pelvic pain returns earlier. In the most recent review by the Data Safety and Monitoring Board (DSMB), the study was stopped early because those treated with raloxifene experienced return of pain significantly sooner than those taking placebo and had 2nd surgery sooner. At that time, 93 of 127 women who had undergone surgery had biopsy positive endometriosis and were randomized. In the next year we will analyze the study outcome results including the effect of raloxifene on menstrual cycle length and adverse events during treatment. It appears that raloxifene taken after complete excision of endometriosis significantly shortened the time to return of pain. [unreadable] [unreadable] As part of this clinical trial, we have explored other aspects of endometriosis. We have previously shown that in comparing surgical and histopathologic findings, only about 70% of endometriosis lesions seen at surgery are biopsy proven. We have recently postulated that different lesion characteristics may correlate with positive histology for endometriosis. Wide, deep, mixed color lesions in the cul-de-sac, ovarian fossa or the utero-sacral ligaments had the highest frequency of endometriosis. Overall, it appears that single color lesions had similar frequencies of biopsy-confirmed endometriosis (59 to 62%), and only lesions with multiple colors had a significantly higher percentage of positive biopsies (76%). Over half of subtle lesions or women with only subtle lesions had endometriosis. We also are developing a predictive logistic regression model by using individual and lesion characteristics that might help surgeons choose lesions that would subsequently be shown to contain histologically confirmed endometriosis. [unreadable] [unreadable] The increased rate of subfertility in women with minimal endometriosis and lower pregnancy rates in women undergoing IVF suggest that the endometrium of these women may not be normally receptive to a blastocyst. We have hypothesized that expression of biomarkers associated with implantation (glycodelin A, osteopontin, lysophosphatidic acid receptor 3, and Homeobox 10A) may be altered in the mid to late luteal phase eutopic endometrium of women with endometriosis compared to normal controls. Preliminary analysis has suggested that the expression of these four biomarkers of implantation is decreased. As many of these markers are progesterone-dependent, these findings suggest the possibility of reduced endometrial progesterone action in this population. [unreadable] [unreadable] Migraine headaches and chronic pelvic pain associated with endometriosis, commonly affect reproductive aged women. We have recently hypothesized that these two chronic, debilitating conditions might co-occur. In our preliminary review of patients enrolled in the clinical trial, at least two thirds of women with chronic pelvic pain have migraine headaches that appear to be independent of endometriosis diagnosis. We will examine whether quality-of-life is lowered, beyond that due to pelvic pain alone. If migraine headache is common in women with chronic pelvic pain, regardless of the presence of endometriosis, it may contribute to disability of those with both conditions and may suggest a common pathophysiology.